White Brain Lesions

[nannysbaby]

Does anyone know, do the white brain lesions found in Sjogren's/MS patients show up on CT scans or does it only show up on MRI's?

[litliwlowa]

I don't know if they show up on CT's. My last brain CT radiology report (dec 2012) only stated nothing acute. It may depend on how the doctor writes the order. The doctor who ordered it was specifically looking for anything acute.

Typically, when my doctors want to check for brain lesions and subsequently check status on my white matter lesions, the choice has been consistently MRI, W & WO contrast.

[nannysbaby]

Thanks.  I was reading earlier on the threads concerning enzymes/itching and all the scientific info and the referral was made to research showing these lesions are associated with Sjogren's.  I had only heard of them being associated with MS.  My sister has them and the drs. thought she might have MS.  Now I am wondering if I might have them also.  I have had a CT scan of my head 5 years ago for a major headache.  I never had a headache like that one!  I hope I never do again!  It was around that time I got the dx for Sjogren's although I did not see that as anything primarily associated with my dx (the headache, that is).  I always believed that if there was anything wrong the dr. would follow up.  Now I am wondering if I should try to find out if he could see anything like that, but if MRI is the only way to see them, then I would be wasting everyone's time.  Sometimes I believe my sis does have MS or some type of AI thing going on.  She had an episode of falling and not being able to walk and some episodes of shakiness that was quite severe.  She started to follow up, but then gave up due to no insurance and family problems.  I try to encourage her to go to the dr. although she has not had any more episodes like the ones I described.

I also have essential tremor which slowly seems to be worsening.  I have not had to do anything about it (yet), but one day I will if I am going to be able to get anything done or write down anything.  It's very annoying!

Thanks for answering my post.  Have a great evening!

[Nat]

Hi nannysbaby~White matter lesions are also associated with numerous other autoimmune diseases, such as celiac disease and rheumatoid arthritis. Research has found that patients with CFS and Alzheimers also have white matter lesions.

For instance, in the study entitled ?Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients? seventy-five patients with biopsy proven CD were tested for neurologic complications. Ten patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development. White matter lesions were detected in 15 patients (20%). The study concluded, ?Focal white matter lesions in the brain may represent an extraintestinal manifestation of celiac disease? (Kieslich, 2001).

So, you would have to look at what all of these diseases have in common that would lead to white matter lesions. The common denominator between all of these diseases is an inability to properly metabolize vitamin B12, due to a lack of the enzymes responsible for the "binding and transport" of vitamin B12-protease. Vitamin B12 helps maintain the myelin sheath by playing a crucial role in the metabolism of fatty acids essential for the maintenance of the myelin.

I have recently posted studies to show that patients with MS and Sjogrens lack vitamin B12. Patients with celiac disease are also deficient in vitamin B12. The study entitled ?Low serum vitamin B12 is common in celiac disease and is not due to autoimmune gastritis? concluded, ?Low B12 is common in celiac disease without concurrent pernicious anemia, and may be a presenting manifestation? (Dickey, 2002).

Here is one of the studies I have in my book on the association between vitamin B12 and white matter lesions.


"In our next study published in Journal of the Neurological Sciences the study authors discussed the neurological manifestations of a vitamin B12 deficiency, which are all consistent with pathological findings and symptoms of MS. These manifestations include demyelination, axonal degeneration and death, spinal cord degeneration, and such common MS symptoms as Lhermitte?s sign, optic neuropathy, paresthesias (abnormal sensations), and white matter lesions.

Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.
Miller A, Korem M, Almog R, Galboiz Y. 2005. J Neurol Sci. 233(1-2):93-7.


"low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders?Vitamin B12 deficiency leads to defective formation of the myelin sheath, due to incorporation into neuronal lipids of non-physiologic fatty acids as well as to defective methylation of myelin basic protein, a major component of CNS myelin?The neurologic manifestations [of vitamin B12 deficiency] begin pathologically with demyelination, followed by axonal degeneration and eventual irreversible damage due to axonal death. The spinal cord, brain, optic nerves, and peripheral nerves may all be affected by cobalamin deficiency. The spinal cord is usually affected first?The patient first notices general weakness and paresthesias. As the illness progresses the gait becomes unsteady and stiffness and weakness of the limbs develop, as well as ataxic paraplegia. The Lhermitte phenomenon is not an uncommon finding. Mental signs are frequent and range from irritability, apathy, somnolence and emotional instability to marked confusional or depressive states. Visual impairment due to optic neuropathy may occasionally be the earliest or sole manifestation?In a study evaluating the neuro-physiological and magnetic resonance imaging (MRI) changes in patients presenting with vitamin B12 deficiency and neurological syndromes, the evoked potentials and MRI changes were found to be consistent with focal demyelination of white matter in the spinal cord and optic nerve. MRI imaging of the brain and spinal cord demonstrates, in some cases of vitamin B12 deficiency, a typical pattern of white matter degeneration commonly seen in MS, such as extensive areas of T2 high-intensity signal in the periventricular white matter?"

[Nat]

Also, here is a link to a study that demonstrates the association between Alzheimer's disease and white matter lesions.

http://jnnp.bmj.com/content/76/9/1286

I think Alzheimer's disease is just a later stage development of missing protease. For instance, in the following study the researchers stated that there is increasing evidence for an association between Alzheimer's disease and "nutritionally independent" cobalamin (vitamin B12) deficiency. The researchers believe this may be due to a "protease" inhibition, a common factor in Alzheimer?s disease. The lack of protease results in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
McCaddon, A., B. Regland, C.F. Fear. 1995. Med Hypotheses. 45(2):200-4.

"There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology?This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism."

[nannysbaby]

Nat, Thanks for responding to my question.  My father had AD.  I wonder, can supplements help or did I read in another one of your posts that the situation would exist even if you took supplements of the B-12 or enzymes? In other words it's something that cannot be fixed, right?  I know much smarter people than me would have already jumped on that answer by now.  Are we all grasping at straws with supplementation?  I don't recall my dad taking anything except a multi-vitamin, but he took around 17 other meds before he died.  He had other serious complicated diseases also (he did live a long life though-91).  But after the dimentia took over all he did for two years was sit in a wheel chair.  It was very sad.  My mom on the other hand is 94 and her mind is better than my brain-fogged gray matter.  I tell her that all the time, but she refuses just because she is 94 and I am 66.  There is not much she does not remember--it amazes me.  She only goes to the dr. once/year because he insists. LOL  But I know the inevitable has to come.  I am happy she can enjoy her life and stay up to date with the family, etc., and that I get to be with her at this time.

[Nat]

The lack of vitamin B12 in autoimmune disease is due to an inability to properly metabolize the vitamin because of the missing enzymes protease and DNase 1.  Let me show you another example of how these missing enzymes would lead to a "cellular" deficiency of vitamin B12.

Here is a study that shows patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis)have significantly lower DNase 1. 

Autoimmune Dis. 2011;2011:945861. doi: 10.4061/2011/945861. Epub 2011 May 29.
Impaired deoxyribonuclease I activity in patients with inflammatory bowel diseases.

Mal?čkov? K, Duricov? D, Bortl?k M, Hru?kov? Z, Svobodov? B, Machkov? N, Kom?rek V, Fuč?kov? T, Janatkov? I, Zima T, Luk?? M.

"Results. DNase I activity in IBD patients was significantly lower than in healthy individuals..."



Since protease and DNase 1 are needed  for the proper metabolism of vitamin B12, we would expect to find white matter lesions in patients with IBS.

Here is a study that confirms this.

http://www.ncbi.nlm.nih.gov/pubmed/21091817


Here is a study entitled "Crohn's disease and vitamin B12 metabolism" that concluded Crohn's disease patients may have altered "intracellular" vitamin B12 status.

http://www.ncbi.nlm.nih.gov/pubmed/8689919

So, the reason autoimmune patients lack vitamin B12 is due to an inability to properly metabolize the vitamin into normal healthy cells, due to missing enzymes.   Taking supplements will not restore your body's ability to metabolize vitamin B12.


The situation is far from hopeless though. Quite the contrary. If DNase 1 and protease were restored, your body would then be able to properly metabolize vitamin B12. These enzymes also digest proteins and release essential amino acids, among other vital functions, so it is imperative they be restored.

They can easily be replaced through diet. You would need to also heal your GI tract and avoid anything that might do further harm to these enzymes or your GI tract.  I completely recovered from lupus, CFS, and fibro by healing my GI tract and replacing these enzymes through diet alone.

[BKreader]

Mine never showed on CT just MRI.

[SjoAmy]

Also, here is a link to a study that demonstrates the association between Alzheimer's disease and white matter lesions.

http://jnnp.bmj.com/content/76/9/1286

I think Alzheimer's disease is just a later stage development of missing protease. For instance, in the following study the researchers stated that there is increasing evidence for an association between Alzheimer's disease and "nutritionally independent" cobalamin (vitamin B12) deficiency. The researchers believe this may be due to a "protease" inhibition, a common factor in Alzheimer?s disease. The lack of protease results in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
McCaddon, A., B. Regland, C.F. Fear. 1995. Med Hypotheses. 45(2):200-4.

"There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology?This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism."

Nat,

Have you found any Sjogren's patients with Alpha 1 Antitripsyin Deficiency?  If so, what % roughly?

Do BCAAs help Alpha 1 Anti-Trypsin Deficiency?

My memory problems could hypothetically  come from my body being unable to assimilate B vitamins.....despite my supplementation of them.

Does Protease deficiency then go hand in hand with MTHFR deficiency?

(methylhydrofolate reductase)


Thank you Nat!

[Nat]

Hi SjoAmy~

Sorry, I haven't done any research on Alpha 1 Antitripsyin Deficiency.

For a person with autoimmune disease, taking supplemental BCAA's could be harmful.

If you lack the ability to properly metabolize proteins, not only would you be deprived of the amino acids and vitamin B12 found in those proteins, but the components of which those proteins are comprised (amino acids) would enter the bloodstream and trigger an immune response.

Here is a picture of these unbroken down protein particles in a lupus patients bloodstream. (Notice the last paragraph where it states lupus patients lack the enzyme DNase 1)

http://www.sciencedaily.com/releases/2010/05/100503161423.htm

Taking additional amino acids in supplement form would lead to an increased risk of disease. This is evident in the findings from a study entitled ?Intermediary metabolism of phenylalanine and tyrosine in diffuse collagen diseases? (Nishimura, 1959). When lupus patients were given supplements of tyrosine and phenylalanine, the supplements ?unfailingly aggravated both clinical signs and laboratory data of collagen disease.?

I think this is one of the strongest lesions that can be learned about autoimmune disease--you shouldn't take supplemental nutrients into your body that you have lost the ability to properly metabolize-even if you lack them. They will just do as the researchers stated in the lupus study-unfailingly aggravate both clinical signs and laboratory data of the disease. The nutrients that are lacking in patients with autoimmune disease--amino acids, vitamin B12, zinc, iron, calcium, magnesium, and vitamin D are all lacking because the body has lost the ability to properly metabolize them.

I can address your question about the MTHFR deficiency in the next post.

[nannysbaby]

This is so interesting and yet intricate and complicated.  Bottom line that may be why the drs don't rx more supplementation then because it could exacerbate the original problems.  Better to educate on the right foods to eat and get better nutrition and approach the problem from that direction.  So by plugging the holes in your diet you were able to completely get over your illnesses or their symptoms?  That is so wonderful! 

When I first got my dx for pSS I felt like it was just dry mouth and dry eyes and wasn't all that.  Two years later a nurse recommended I read a book about AI diseases (I guess she sensed that I was not taking it seriously enough).  I did, and the longer I search and try to learn more, the more it brings me to my knees.  It is so serious!  Not long ago I saw a video of a dr. on You Tube who had MS and cured herself of her symptoms of MS.  At the time I did not feel that particularly applied to me in any way, but with what I am learning here now concerning the white brain lesions and the inabilities of our bodies to metabolize correctly, it makes me think we are all connected and perhaps one has MS and another has Lupus and another has Sjogren's, but we are all different branches connected to the same trunk of the tree (if that makes sense).  We all have one disease (AI) and demonstrate differing symptoms based on our unique individual makeup.  If I am misunderstanding, please correct me Nat and thank you for including these research locations.  I believe I will relook at that video.

[Nat]

Hi SjoAmy~

I wanted to address your comment about memory problems next. Autoimmune disease patients all share the same exact underlying disease pathway that originates with missing enzymes called protease and DNase 1. These enzymes digest dietary proteins and release essential amino acids. A lack of these enzymes would lead to a lack of essential amino acids.  I have been posting studies that show autoimmune patients lack essential amino acids--one of which is phenylalanine.


The essential amino acid phenylalanine is needed to produce dopamine (Phenylalanine>Tyrosine>Dopamine) A lack of dopamine would lead to brain gray matter loss.

In the following study published in The Journal of Pain researchers found a strong correlation between dopamine metabolism and gray matter density.


Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism.
Wood, P.B., M.F. Glabus, R. Simpson, J.C. Patterson 2nd. 2009. J Pain 10(6):609-18. Epub 2009 Apr 23.

"Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes."


The gray matter involves regions of the brain concerned with muscle control, emotions, learning and MEMORY, speech, and sensory perception such as seeing and hearing. In the following study published in Neurology the researchers stated that gray matter atrophy is detected even in the earliest stages of MS.


Gray matter involvement in multiple sclerosis.
Pirko I, Lucchinetti CF, Sriram S, Bakshi R. 2007. Neurology. 68(9):634-42.


"Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression?"



In the following study the researchers concluded that patients with Sjogren's syndrome had decreased brain gray matter.

CNS involvement in primary Sjogren?s syndrome: assessment of gray and white
matter changes with MRI and voxel-based morphometry.
Tzarouchi, L.C., N. Tsifetaki, S. Konitsiotis, A. Zikou, L. Astrakas, A. Drosos, M.I. Argyropoulou. 2011. AJR Am J Roentgenol.197(5):1207-12. doi: 10.2214/AJR.10.5984.

"?In comparison with the controls, patients with primary Sj?gren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum?"


Researchers in the following study discovered that the gray matter (GM) was "particularly affected" in patients with neuropsychiatric lupus (NPSLE).

Selective gray matter damage in neuropsychiatric lupus.
Steens, S.C., F. Admiraal-Behloul, G.P. Bosma, G.M. Steup-Beekman, H. Olofsen, S. Le Cessie, T.W. Huizinga, M.A. Van Buchem. 2004. Arthritis Rheum. 50(9):2877-81.

"?This is the first study to demonstrate? that in SLE patients with a history of NP symptoms ?the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE."

How bad is it to have brain gray matter loss due to a lack of dopamine? In the following study published in the Journal of Neuroscience researchers found that the longer the individuals had fibromyalgia, the greater the brain gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging.

Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?
Kuchinad, A. P. Schweinhardt, D.A. Seminowicz, P.B. Wood, B.A. Chizh, M.C. Bushnell. 2007. J Neurosci 11;27(15):4004-7.

"We found that fibromyalgia patients had significantly less total gray matter volume and showed a 3.3 times greater age-associated decrease in gray matter than healthy controls. The longer the individuals had had fibromyalgia, the greater the gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging."

[lighthouse33]

A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT

http://stroke.ahajournals.org/content/32/6/1318.long

Imaging in Progressive Multifocal Leukodystrophy

Progressive multifocal leukoencephalopathy (PML) is a fatal subacute progressive demyelinating disease seen in persons with impaired cell-mediated immune response. PML predominantly occurs in patients with acquired immunodeficiency syndrome (AIDS). Before the AIDS epidemic, PML was rare and associated with other immunocompromised conditions, such as leukemia, lymphoma, systemic lupus erythematosus (SLE), organ transplantation, Wiskott-Aldrich syndrome, and severe combined immunodeficiency (SCID).

MRI is the preferred diagnostic imaging modality. It is sensitive to white matter lesions and shows hyperintense lesions on T2-weighted (T2W) images in affected regions. Because of its superior contrast resolution, it can be used to detect subtle white matter abnormalities, whereas CT depicts the lesions at an advanced stage.

http://emedicine.medscape.com/article/343475-overview

[finallyadx]

I have brain lesions and was told it is due (probably - not a definitive answer by the neuro I saw) from sjogrens but could also be caused continued migraine headaches or other headaches.  I must say I was quite concerned when the neurologist called me a year ago to tell me this...so many things ran through my mind.   

I hope you are able to find some answers.

Sending positive thought your way.

[nannysbaby]

Thank you Lighthouse 33.  I thought the information you cited was very interesting and for sure it answers the question without any doubt.

Thank you Finallyadx for taking the time to respond.  Sorry to hear you have lesions.  Do you have cognitive problems associated with Sjogren's.  I do.  Lately it worries me a lot and I intend to bring it up with my rheum on the next visit.  (He probably already knows.  I say that because sometimes when he asks how I've been doing I feel like I don't know where to start and I hesitate a couple of times I really went blank.)  He never said anything and neither did I, but I think I am including it on my list this time just so he is aware.